Basolateral PAR‐2 receptors mediate KCl secretion and inhibition of Na+ absorption in the mouse distal colon

Abstract
Proteinase-activated receptor-2 (PAR-2) may participate in epithelial ion transport regulation. Here we examined the effect of mouse activating peptide (mAP), a specific activator of PAR-2, on electrogenic transport of mouse distal colon using short-circuit current (ISC) measurements. Under steady-state conditions, apical application of amiloride (100 μm) revealed a positive ISC component of 74.3 ± 6.8 μA cm−2 indicating the presence of Na+ absorption, while apical Ba2+ (10 mm) identified a negative ISC component of 26.2 ± 1.8 μA cm−2 consistent with K+ secretion. Baseline Cl secretion was minimal. Basolateral addition of 20 μm mAP produced a biphasic ISC response with an initial transient peak increase of 11.2 ± 0.9 μA cm−2, followed by a sustained fall to a level 31.2 ± 2.6 μA cm−2 (n = 43) below resting ISC. The peak response was due to Cl secretion as it was preserved in the presence of amiloride but was largely reduced in the presence of basolateral bumetanide (20 μm) or in the absence of extracellular Cl. The secondary decline of ISC was also attenuated by bumetanide and by Ba2+, indicating that it is partly due to a stimulation of K+ secretion. In addition, the amiloride-sensitive ISC was slightly reduced by mAP, suggesting that inhibition of Na+ absorption also contributes to the ISC decline. Expression of PAR-2 in mouse distal colon was confirmed using RT-PCR and immunocytochemistry. We conclude that functional basolateral PAR-2 is present in mouse distal colon and that its activation stimulates Cl and K+ secretion while inhibiting baseline Na+ absorption.

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